University of Groningen
AMP and adenosine induced dyspnea perception associated to large and small airways dysfunction in asthma
Hagedoorn, Paul
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2018
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Hagedoorn, P. (2018). AMP and adenosine induced dyspnea perception associated to large and small airways dysfunction in asthma. 1. Poster session presented at Annual Conference, European Respiratory Society, .
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
Introduction
Bronchial provocation is often used to diagnose asthma or monitor disease control. Dyspnea perception, however, associates poorly with the induced drop in FEV1. Some subjects perceive dyspnea well before the drop, while others perceive non. This discrepancy may arise from the origin of dyspnea. As a provocation
test solely uses the large airways parameter FEV1, although dyspnea is associated with both large- and small airways dysfunction.
Aims
We explored if induced dyspnea perception is equal for nebulized adenosine 5’-monophosphate (AMP) and dry powder adenosine, targeting large and small
airways, respectively. Further we investigated if dyspnea perception associates better with large or small airways dysfunction.
Methods
For this study, we used the baseline data of the previously published OLiVIA study1, in which asthmatics performed an AMP and an adenosine provocation.
All 59 subjects performed spirometry, impulse oscillometry (IOS), and Borg dyspnea score, of whom 36 completed a multiple breath nitrogen washout (MBNW). Spearman’s correlation analysis was used to associate the change(Δ) in Borg score to the change in large and small airways parameters. To construct a linear multivariate regression model a large and a small airways parameter2 was selected (lowest p-value) from spirometry and IOS. MBNW was analyzed separately. Results
• Provocation with adenosine and AMP evoked a decreases in FEV1 of 23.4±8% and 21.1±8%, respectively.
This corresponded with similar levels of induced dyspnea (Figure 1). ΔBorg did not associated with ΔFEV1 for neither adenosine nor AMP provocation.
• ΔBorg after adenosine provocation associated with a decrease in FEF25 (p=0.01), FEF75 (p<0.01), and FEF25-75 (p<0.01, Figure 2)
and in the multivariate linear regression model (Table 2a) a decrease in FEF25-75 was independently associated with an increase in Borg.
• ΔBorg after AMP provocation associated univariately with an increased AX (p=0.05) and a decreased X5 (p=0.04, Figure 3),
but in the multivariate analyses no independent associations were found between ΔBorg and any large or small airways parameters (Table 2b).
Conclusions
• AMP and adenosine induce equally severe dyspnea perception.
• Dry powder adenosine-induced dyspnea seems related to small airways involvement independent of the large airways.
• AMP-induced dyspnea associates with neither large nor small airways dysfunction.
• Our results may indicate that dry powder adenosine and nebulized AMP induce dyspnea via different processes.
GRONINGEN RESEARCH INSTITUTE FOR ASTHMA AND COPD
References
1. Cox, C. A. et al. Respir. Med. (2017).
2. Van Der Wiel, E. J. Allergy Clin. Immunol. (2013). Authors:
Claire A. Coxa,b
Ilse M. Boudewijna,b
Sebastiaan J. Vroegopc
Siebrig Schokkerc
Anne J. Lexmondd
Henderik W. Frijlinkd
Paul Hagedoornd
Judith M. Vonkb,e
Martijn P. Farenhorsta
Nick H. T. ten Hackena,b
Huib A.M. Kerstjensa,b
Maarten van den Bergea,b
Affiliations:
a. University Medical Center Groningen, Department of Pulmonology,
Groningen, The Netherlands b. University of Groningen,
University Medical Center Groningen Research
Institute for Asthma and COPD, Groningen, The Netherlands
c. Martini Hospital Groningen,
Groningen, The Netherlands d. University of Groningen,
Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands e. University of Groningen,
Department of Epidemiology, Groningen, The Netherlands Contact:
c.a.cox@umcg.nl
m.van.den.berge@umcg.nl
The study was supported by a research grant from TEVA pharmaceu�cal Industries Ltd
Table 1: Baseline characteristics
count or median (IQR)
Gender (M-F) 24 - 35 Age (years) 47.0 (37.0; 55.0) Smoking (Current-Ex) 30 - 29 Pack-years (years) 16.8 (11.0; 26.0) Adenosine provocation (mg) 3.11 (0.87; 6.38) AMP provocation (mg mL-1) 14.67 (4.7; 44.88) FEV1 (%pred) 85 (74; 96) FVC (%pred) 105 (94; 116) FEV1/FVC (%) 70 (62; 77) FEF25-75(%pred) 49 (35; 65) R5(kPa sL-1) 0.53 (0.42; 0.67) R20 (kPa sL-1) 0.42 (0.35; 0.47) AX (kPa L-1) 0.64 (0.24; 1.82) X5(kPa sL-1) -0.13 (-0.22; -0.09) LCI5% 6.22 (5.76; 7.37) Scond 0.04 (0.02; 0.06) Sacin 0.14 (0.10; 0.19)
Table 2: Multivariate models for ΔBorg
All subjects MBNW subgroup A. Adenosine B (p-value) B (p-value) Gender -0.83 (0.37) -0.81 (0.37) Smoking status 0.32 (0.65) 0.45 (0.51) Δ FEV1(L) 1.50 (0.43) 0.98 (0.60) Δ FEF25-75 (Ls-1) -2.18 (0.04) -1.82 (0.09) Δ R20 (kPa sL-1) -8.28 (0.11) -6.53 (0.20) Δ R5-R20 (kPa sL-1) 2.61 (0.27) 3.20 (0.18) Δ Scond 14.56 (0.16) B. AMP B (p-value) B (p-value) Gender 0.25 (0.78) 0.55 (0.62) Smoking status -0.11 (0.90) -0.23 (0.81) Δ FEV1(L) -0.97 (0.62) -0.74 (0.72) Δ FEF50 (Ls-1) 0.50 (0.54) 0.60 (0.48) Δ R20 (kPa sL-1) -2.00 (0.76) -1.01 (0.88) Δ X5 (kPa sL-1) -0.64 (0.67) -0.69 (0.65) Δ LCI5% 0.22 (0.65)
AMP and adenosine induced dyspnea perception
associated to large and small airways dysfunction in asthma
Figure 1: Changes in Borg score (ΔBorg)
from pre-provocation to post-provocation for adenosine and AMP. Both agents increase dyspnea perception to the same degree.
Figure 2: Correlation of change(Δ) in Borg and FEF25-75.
Adenosine(♦) induced ΔBorg correlates with ΔFEF25-75, while
AMP(●) induced ΔBorg lacks a correlation.
Figure 3: Correlation of change(Δ) in Borg and X5
AMP(●) induced ΔBorg correlates with ΔX5, while adenosine(♦)
induced ΔBorg lacks a correlation.
0 2 4 6 8 10 Borg (points)
pre Adenosine post pre AMP post
p=0.65 0 1 2 3 4 5 6 7 8 9 10 í5 í í5 í í5 0 5 ¨ FEF í , (L) ¨ Borg $GHQRVLQHUKR íS $03UKR íS 0 1 2 3 4 5 6 7 8 9 10 í í8 í6 í4 í2 0 2 ¨ X5, (kPa sL í ) ¨ Borg $GHQRVLQHUKR íS $03UKR íS
